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Contribution of phenylalanine side chain intercalation to the TATA-box binding protein–DNA interaction: molecular dynamics and dispersion-corrected density functional theory studies

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Abstract

Deformation of DNA takes place quite often due to binding of small molecules or proteins with DNA. Such deformation is significant due to minor groove binding and, besides electrostatic interactions, other non-covalent interactions may also play an important role in generating such deformation. TATA-box binding protein (TBP) binds to the minor groove of DNA at the TATA box sequence, producing a large-scale deformation in DNA and initiating transcription. In order to observe the interactions of protein residues with DNA in the minor groove that produce the deformation in the DNA structure, we carried out molecular dynamics simulations of the TBP–DNA system. The results reveal consistent partial intercalation of two Phe residues, distorting stacking interactions at two dinucleotide step sites. We carried out calculations based on dispersion-corrected density functional theory to understand the source of such stabilization. We observed favorable interaction energies between the Phe residues and the base pairs with which they interact. We suggest that salt-bridge interactions between the phosphate groups and Lys or Arg residues, along with the intercalation of Phe residues between two base pair stacks, stabilize the kinked and opened-up DNA conformation.

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References

  1. Reha D, Kabelac M, Ryjacek F, Sponer J, Sponer JE, Elstner M, Suhai S, Hobza P (2002) Intercalators. 1. Nature of stacking interactions between intercalators (ethidium, daunomycin, ellipticine, and 4 ′,6-diaminide-2-phenylindole) and DNA base pairs. Ab initio quantum chemical, density functional theory, and empirical potential study. J Am Chem Soc 124(13):3366–3376. doi:10.1021/Ja011490d

    Article  CAS  Google Scholar 

  2. Geierstanger BH, Wemmer DE (1995) Complexes of the minor groove of DNA. Annu Rev Biophys Biomol Struct 24:463–493. doi:10.1146/annurev.bb.24.060195.002335

    Article  CAS  Google Scholar 

  3. Rentzeperis D, Marky LA, Dwyer TJ, Geierstanger BH, Pelton JG, Wemmer DE (1995) Interaction of minor groove ligands to an AAATT/AATTT site: correlation of thermodynamic characterization and solution structure. Biochemistry 34(9):2937–2945. doi:10.1021/bi00009a025

    Article  CAS  Google Scholar 

  4. Wemmer DE (2000) Designed sequence-specific minor groove ligands. Annu Rev Biophys Biomol Struct 29:439–461. doi:10.1146/annurev.biophys.29.1.439

    Article  CAS  Google Scholar 

  5. Peek ME, Lipscomb LA, Haseltine J, Gao Q, Roques BP, Garbay-Jaureguiberry C, Williams LD (1995) Asymmetry and dynamics in bis-intercalated DNA. Bioorg Med Chem 3(6):693–699. doi:10.1016/0968-0896(95)00064N

    Article  CAS  Google Scholar 

  6. Zimmer C, Wahnert U (1986) Nonintercalating DNA-binding ligands: specificity of the interaction and their use as tools in biophysical, biochemical and biological investigations of the genetic material. Prog Biophys Mol Biol 47(1):31–112. doi:10.1016/0079-6107(86)90005-2

    Article  CAS  Google Scholar 

  7. de Pascual-Teresa B, Gallego J, Ortiz AR, Gago F (1996) Molecular dynamics simulations of the bis-intercalated complexes of ditercalinium and Flexi-Di with the hexanucleotide d(GCGCGC)2: theoretical analysis of the interaction and rationale for the sequence binding specificity. J Med Chem 39(24):4810–4824. doi:10.1021/jm9604179

    Article  Google Scholar 

  8. Gallego J, Ortiz AR, de Pascual-Teresa B, Gago F (1997) Structure-affinity relationships for the binding of actinomycin D to DNA. J Comput Aided Mol Des 11(2):114–128. doi:10.1023/A:1008018106064

    Article  CAS  Google Scholar 

  9. Gago F (1998) Stacking interactions and intercalative DNA binding. Methods 14(3):277–292. doi:10.1006/meth.1998.0584

    Article  CAS  Google Scholar 

  10. Kolar M, Kubar T, Hobza P (2010) Sequence-dependent configurational entropy change of DNA upon intercalation. J Phys Chem B 114(42):13446–13454. doi:10.1021/jp1019153

    Article  CAS  Google Scholar 

  11. Baker CM, Grant GH (2007) Role of aromatic amino acids in protein-nucleic acid recognition. Biopolymers 85(5–6):456–470. doi:10.1002/bip.20682

    Article  CAS  Google Scholar 

  12. Juo ZS, Chiu TK, Leiberman PM, Baikalov I, Berk AJ, Dickerson RE (1996) How proteins recognize the TATA box. J Mol Biol 261(2):239–254. doi:10.1006/jmbi.1996.0456

    Article  CAS  Google Scholar 

  13. Kim JL, Nikolov DB, Burley SK (1993) Co-crystal structure of TBP recognizing the minor groove of a TATA element. Nature 365(6446):520–527. doi:10.1038/365520a0

    Article  CAS  Google Scholar 

  14. Kim Y, Geiger JH, Hahn S, Sigler PB (1993) Crystal structure of a yeast TBP/TATA-box complex. Nature 365(6446):512–520. doi:10.1038/365512a0

    Article  CAS  Google Scholar 

  15. Nikolov DB, Chen H, Halay ED, Hoffman A, Roeder RG, Burley SK (1996) Crystal structure of a human TATA box-binding protein/TATA element complex. Proc Natl Acad Sci USA 93(10):4862–4867. doi:10.1073/pnas.93.10.4862

    Article  CAS  Google Scholar 

  16. Tan S, Hunziker Y, Sargent DF, Richmond TJ (1996) Crystal structure of a yeast TFIIA/TBP/DNA complex. Nature 381(6578):127–134. doi:10.1038/381127a0

    Article  CAS  Google Scholar 

  17. Geiger JH, Hahn S, Lee S, Sigler PB (1996) Crystal structure of the yeast TFIIA/TBP/DNA complex. Science 272(5263):830–836. doi:10.1126/science.272.5263.830

    Article  CAS  Google Scholar 

  18. Kosa PF, Ghosh G, DeDecker BS, Sigler PB (1997) The 2.1-angstrom crystal structure of an archaeal preinitiation complex: TATA-box-binding protein/transcription factor (II)B core/TATA-box. Proc Natl Acad Sci USA 94(12):6042–6047. doi:10.1073/pnas.94.12.6042

    Article  CAS  Google Scholar 

  19. Nikolov DB, Chen H, Halay ED, Usheva AA, Hisatake K, Lee DK, Roeder RG, Burley SK (1995) Crystal-structure of a Tfiib-Tbp-TATA-element ternary complex. Nature 377(6545):119–128. doi:10.1038/377119a0

    Article  CAS  Google Scholar 

  20. Umezawa Y, Nishio M (2000) CH/pi interactions in the crystal structure of TATA-box binding protein/DNA complexes. Bioorg Med Chem 8(11):2643–2650. doi:10.1016/S0968-0896(00)00197-8

    Article  CAS  Google Scholar 

  21. Nishinaka T, Ito Y, Yokoyama S, Shibata T (1997) An extended DNA structure through deoxyribose-base stacking induced by RecA protein. Proc Natl Acad Sci USA 94(13):6623–6628. doi:10.1073/pnas.94.13.6623

    Article  CAS  Google Scholar 

  22. Nishinaka T, Shinohara A, Ito Y, Yokoyama S, Shibata T (1998) Base pair switching by interconversion of sugar puckers in DNA extended by proteins of RecA-family: a model for homology search in homologous genetic recombination. Proc Natl Acad Sci USA 95(19):11071–11076. doi:10.1073/pnas.95.19.11071

    Article  CAS  Google Scholar 

  23. Strahs D, Barash D, Qian XL, Schlick T (2003) Sequence-dependent solution structure and motions of 13 TATA/TBP (TATA-box binding protein) complexes. Biopolymers 69(2):216–243. doi:10.1002/bip.10409

    Article  CAS  Google Scholar 

  24. Pardo L, Pastor N, Weinstein H (1998) Selective binding of the TATA box-binding protein to the TATA box-containing promoter: analysis of structural and energetic factors. Biophys J 75(5):2411–2421. doi:10.1016/S0006-3495(98)77685-4

    Article  CAS  Google Scholar 

  25. Pastor N, Pardo L, Weinstein H (1997) Does TATA matter? a structural exploration of the selectivity determinants in its complexes with TATA box-binding protein. Biophys J 73(2):640–652. doi:10.1016/S0006-3495(97)78099-8

    Article  CAS  Google Scholar 

  26. Starr DB, Hoopes BC, Hawley DK (1995) DNA bending is an important component of site-specific recognition by the TATA binding protein. J Mol Biol 250(4):434–446. doi:10.1006/jmbi.1995.0388

    Article  CAS  Google Scholar 

  27. Patikoglou GA, Kim JL, Sun LP, Yang SH, Kodadek T, Burley SK (1999) TATA element recognition by the TATA box-binding protein has been conserved throughout evolution. Genes Dev 13(24):3217–3230. doi:10.1101/gad.13.24.3217

    Article  CAS  Google Scholar 

  28. Wong JM, Bateman E (1994) TBP-DNA interactions in the minor groove discriminate between A:T and T:A base pairs. Nucleic Acids Res 22(10):1890–1896. doi:10.1093/nar/22.10.1890

    Article  CAS  Google Scholar 

  29. Zhao Y, Truhlar DG (2008) The M06 suite of density functionals for main group thermochemistry, thermochemical kinetics, noncovalent interactions, excited states, and transition elements: two new functionals and systematic testing of four M06-class functionals and 12 other functionals. Theor Chem Acc 120(1–3):215–241. doi:10.1007/s00214-007-0310-x

    Article  CAS  Google Scholar 

  30. Zhao Y, Truhlar DG (2008) Density functionals with broad applicability in chemistry. Acc Chem Res 41(2):157–167. doi:10.1021/Ar700111a

    Article  CAS  Google Scholar 

  31. Hohenstein EG, Chill ST, Sherrill CD (2008) Assessment of the performance of the M05-2X and M06-2X exchange-correlation functionals for noncovalent interactions in biomolecules. J Chem Theory Comput 4(12):1996–2000. doi:10.1021/Ct800308k

    Article  CAS  Google Scholar 

  32. Hargis JC, Schaefer HF, Houk KN, Wheeler SE (2010) Noncovalent Interactions of a Benzo[a]pyrene diol epoxide with DNA base pairs: insight into the formation of adducts of (+)-BaP DE-2 with DNA. J Phys Chem A 114(4):2038–2044. doi:10.1021/Jp911376p

    Article  CAS  Google Scholar 

  33. Goerigk L, Grimme S (2011) A thorough benchmark of density functional methods for general main group thermochemistry, kinetics, and noncovalent interactions. Phys Chem Chem Phys 13(14):6670–6688. doi:10.1039/C0cp02984j

    Article  CAS  Google Scholar 

  34. Sedlak R, Janowski T, Pitonak M, Rezac J, Pulay P, Hobza P (2013) Accuracy of quantum chemical methods for large noncovalent complexes. J Chem Theory Comput 9(8):3364–3374. doi:10.1021/Ct400036b

    Article  CAS  Google Scholar 

  35. Mukherjee S, Kailasam S, Bansal M, Bhattacharyya D (2014) Energy hyperspace for stacking interaction in AU/AU dinucleotide step: dispersion-corrected density functional theory study. Biopolymers 101(1):107–120. doi:10.1002/Bip.22289

    Article  CAS  Google Scholar 

  36. Svozil D, Hobza P, Sponer J (2010) Comparison of intrinsic stacking energies of ten unique dinucleotide steps in A-RNA and B-DNA duplexes. can we determine correct order of stability by quantum-chemical calculations? J Phys Chem B 114(2):1191–1203. doi:10.1021/jp910788e

    Article  CAS  Google Scholar 

  37. Morgado CA, Jurecka P, Svozil D, Hobza P, Sponer J (2010) Reference MP2/CBS and CCSD(T) quantum-chemical calculations on stacked adenine dimers. comparison with DFT-D, MP2.5, SCS(MI)-MP2, M06-2X, CBS(SCS-D) and force field descriptions. Phys Chem Chem Phys 12(14):3522–3534. doi:10.1039/b924461a

    Article  CAS  Google Scholar 

  38. Ford AR, Janowski T, Pulay P (2007) Array files for computational chemistry: MP2 energies. J Cmput Chem 28(7):1215–1220. doi:10.1002/jcc.20630

    Article  CAS  Google Scholar 

  39. Morgado C, Vincent MA, Hillier IH, Shan X (2007) Can the DFT-D method describe the full range of noncovalent interactions found in large biomolecules? Phys Chem Chem Phys 9(4):448–451. doi:10.1039/b615263e

    Article  CAS  Google Scholar 

  40. Cooper VR, Thonhauser T, Puzder A, Schroder E, Lundqvist BI, Langreth DC (2008) Stacking interactions and the twist of DNA. J Am Chem Soc 130(4):1304–1308. doi:10.1021/ja0761941

    Article  CAS  Google Scholar 

  41. Grimme S (2004) Accurate description of van der Waals complexes by density functional theory including empirical corrections. J Comput Chem 25(12):1463–1473. doi:10.1002/Jcc.20078

    Article  CAS  Google Scholar 

  42. Chai JD, Head-Gordon M (2008) Long-range corrected hybrid density functionals with damped atom–atom dispersion corrections. Phys Chem Chem Phys 10(44):6615–6620. doi:10.1039/B810189b

    Article  CAS  Google Scholar 

  43. Grimme S, Antony J, Ehrlich S, Krieg H (2010) A consistent and accurate ab initio parametrization of density functional dispersion correction (DFT-D) for the 94 elements H-Pu. J Chem Phys 132:15. doi:10.1063/1.3382344

  44. Hobza P (2012) Calculations on noncovalent interactions and databases of benchmark interaction energies. Acc Chem Res 45(4):663–672. doi:10.1021/ar200255p

    Article  CAS  Google Scholar 

  45. Morgado CA, Svozil D, Turner DH, Sponer J (2012) Understanding the role of base stacking in nucleic acids. MD and QM analysis of tandem GA base pairs in RNA duplexes. Phys Chem Chem Phys 14(36):12580–12591. doi:10.1039/C2cp40556c

    Article  CAS  Google Scholar 

  46. Barone G, Guerra CF, Bickelhaupt FM (2013) B-DNA structure and stability as function of nucleic acid composition: dispersion-corrected DFT Study of dinucleoside monophosphate single and double strands. Chemistryopen 2(5–6):186–193. doi:10.1002/open.201300019

    Article  CAS  Google Scholar 

  47. Parker TM, Hohenstein EG, Parrish RM, Hud NV, Sherrill CD (2013) Quantum-mechanical analysis of the energetic contributions to pi stacking in nucleic acids versus rise, twist, and slide. J Am Chem Soc 135(4):1306–1316. doi:10.1021/Ja30633091

    Article  CAS  Google Scholar 

  48. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE (2000) The protein data bank. Nucleic Acids Res 28(1):235–242. doi:10.1093/nar/28.1.235

    Article  CAS  Google Scholar 

  49. Pearlman DA, Case DA, Caldwell JW, Ross WS, Cheatham TE, Debolt S, Ferguson D, Seibel G, Kollman P (1995) AMBER, a package of computer-programs for applying molecular mechanics, normal-mode analysis. molecular-dynamics and free-energy calculations to simulate the structural and energetic properties of molecules. Comput Phys Commun 91(1–3):1–41. doi:10.1016/0010-4655(95)00041-d

    Article  CAS  Google Scholar 

  50. Cornell WD, Cieplak P, Bayly CI, Gould IR, Merz KM, Ferguson DM, Spellmeyer DC, Fox T, Caldwell JW, Kollman PA (1996) A second generation force field for the simulation of proteins, nucleic acids, and organic molecules. J Am Chem Soc 118(9):5179–5197. doi:10.1021/ja00124a002

    Article  Google Scholar 

  51. Dong C, Yong-Zhi L, Zhi-Chao W, Bo L (2014) Performance of four different force fields for simulations of dipeptide conformations: GlyGly, GlyGly-, GlyGly. Cl-, GlyGly. Na + and GlyGly. (H2O)2. J Mol Model 20(6):2279. doi:10.1007/s00894-014-2279-4

    Article  Google Scholar 

  52. An Y, Raju RK, Lu TX, Wheeler SE (2014) Aromatic interactions modulate the 5 ′-base selectivity of the DNA-binding autoantibody ED-10. J Phys Chem B 118(21):5653–5659. doi:10.1021/Jp502069a

    Article  CAS  Google Scholar 

  53. Kale L, Skeel R, Bhandarkar M, Brunner R, Gursoy A, Krawetz N, Phillips J, Shinozaki A, Varadarajan K, Schulten K (1999) NAMD2: greater scalability for parallel molecular dynamics. J Comput Phys 151(1):283–312. doi:10.1006/jcph.1999.6201

    Article  CAS  Google Scholar 

  54. Nelson M, Humphrey W, Kufrin R, Gursoy A, Dalke A, Kale L, Skeel R, Schulten K (1995) MDSCOPE - a visual computing environment for structural biology. Comput Phys Commun 91(1–3):111–133. doi:10.1016/0010-4655(95)00045-h

    Article  CAS  Google Scholar 

  55. D.A. Case VB, J.T. Berryman, R.M. Betz, Q. Cai, D.S. Cerutti, T.E. Cheatham III, T.A. Darden, R.E. Duke, H. Gohlke, A.W. Goetz, S. Gusarov, N. Homeyer, P. Janowski, J. Kaus, I. Kolossvary, A. Kovalenko, T.S. Lee, S. LeGrand, T. Luchko, R. Luo, B. Madej, K.M. Merz, Jr., F. Paesani, D.R. Roe, A. Roitberg, C. Sagui, R. Salomon-Ferrer, G. Seabra, C.L. Simmerling, W.L. Smith, J. Swails, R.C. Walker, J. Wang, R.M. Wolf, X. Wu, P.A. Kollman (2014) The FF14SB force field. AMBER 14 Reference Manual:29–31

  56. Perez A, Marchan I, Svozil D, Sponer J, Cheatham TE, Laughton CA, Orozco M (2007) Refinenement of the AMBER force field for nucleic acids: improving the description of alpha/gamma conformers. Biophys J 92(11):3817–3829. doi:10.1529/biophysj.106.097782

    Article  CAS  Google Scholar 

  57. Brooks BR, Bruccoleri RE, Olafson BD, States DJ, Swaminathan S, Karplus M (1983) Charmm—a program for macromolecular energy, minimization, and dynamics calculations. J Comput Chem 4(2):187–217. doi:10.1002/jcc.540040211

    Article  CAS  Google Scholar 

  58. Bansal M, Bhattacharyya D, Ravi B (1995) NUPARM and NUCGEN—software for analysis and generation of sequence-dependent nucleic-acid structures. Comput Appl Biosci 11(3):281–287. doi:10.1093/bioinformatics/11.3.281

    CAS  Google Scholar 

  59. Mukherjee S, Majumdar S, Bhattacharyya D (2005) Role of hydrogen bonds in protein–DNA recognition: effect of nonplanar amino groups. J Phys Chem B 109(20):10484–10492. doi:10.1021/Jp0446231

    Article  CAS  Google Scholar 

  60. Roy A, Panigrahi S, Bhattacharyya M, Bhattacharyya D (2008) Structure, stability, and dynamics of canonical and noncanonical base pairs: quantum chemical studies. J Phys Chem B 112(12):3786–3796. doi:10.1021/Jp076921e

    Article  CAS  Google Scholar 

  61. Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, Scalmani G, Barone V, Mennucci B, Petersson GA, Nakatsuji H, Caricato M, Li X, Hratchian HP, Izmaylov AF, Bloino J, Zheng G, Sonnenberg JL, Hada M, Ehara M, Toyota K, Fukuda R, Hasegawa J, Ishida M, Nakajima T, Honda Y, Kitao O, Nakai H, Vreven T, Montgomery JA Jr, Peralta JE, Ogliaro F, Bearpark M, Heyd JJ, Brothers E, Kudin KN, Staroverov VN, Kobayashi R, Normand J, Raghavachari K, Rendell A, Burant JC, Iyengar SS, Tomasi J, Cossi M, Rega N, Millam JM, Klene M, Knox JE, Cross JB, Bakken V, Adamo C, Jaramillo J, Gomperts R, Stratmann RE, Yazyev O, Austin AJ, Cammi R, Pomelli C, Ochterski JW, Martin RL, Morokuma K, Zakrzewski VG, Voth GA, Salvador P, Dannenberg JJ, Dapprich S, Daniels AD, Farkas O, Foresman JB, Ortiz JV, Cioslowski J, Fox DJ (2009) Gaussian, Inc, Wallingford CT

  62. Samanta S, Chakrabarti J, Bhattacharyya D (2010) Changes in thermodynamic properties of DNA base pairs in protein-DNA recognition. J Biomol Struct Dyn 27(4):429–442. doi:10.1080/07391102.2010.10507328

    Article  CAS  Google Scholar 

  63. Dickerson RE (1998) DNA bending: the prevalence of kinkiness and the virtues of normality. Nucleic Acids Res 26(8):1906–1926. doi:10.1093/nar/26.8.1906

    Article  CAS  Google Scholar 

  64. Calladine CR, Drew HR, Luisi BF, Travers AA (2004) Understanding DNA, the molecule and how it works, 3rd edn. Elsevier, London

    Google Scholar 

  65. Halder S, Bhattacharyya D (2013) RNA structure and dynamics: a base pairing perspective. Prog Biophys Mol Biol 113(2):264–283. doi:10.1016/j.pbiomolbio2013.07.003

    Article  CAS  Google Scholar 

  66. Chandrasekaran R, Arnott S (1996) The structure of B-DNA in oriented fibers. J Biomol Struct Dyn 13(6):1015–1027. doi:10.1080/07391102.1996.10508916

    Article  CAS  Google Scholar 

  67. Umezawa Y, Nishio M (2002) Thymine-methyl/pi interaction implicated in the sequence-dependent deformability of DNA. Nucleic Acids Res 30(10):2183–2192. doi:10.1093/nar/30.10.2183

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The authors are thankful to Department of Atomic Energy, Government of India for support through the BARD project.

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  1. Computational Science Division, Saha Institute of Nuclear Physics, 1/AF Bidhan Nagar, Kolkata, 700064, India

    Manas Mondal, Sanchita Mukherjee & Dhananjay Bhattacharyya

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Mondal, M., Mukherjee, S. & Bhattacharyya, D. Contribution of phenylalanine side chain intercalation to the TATA-box binding protein–DNA interaction: molecular dynamics and dispersion-corrected density functional theory studies. J Mol Model 20, 2499 (2014). https://doi.org/10.1007/s00894-014-2499-7

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